The DENAMIC hazard characterisation includes in vitro, ex vivo and in vivo studies using innovative models spanning molecular, cellular and multicellullar (functional) processes, brain slices, brain and behaviour with a focus on neuronal development.
In vitro screening methods for neurotoxicity will be developed and validated with individual model chemicals and mixtures thereof. The focus is on assays for direct cellular neurotoxicity, neuronal function, and neurodevelopment.
To further investigate the mechanism(s) of action of neurotoxic chemicals and validate the in vitro models, ex vivo, in vivo (behavioural) neurotoxicity, and cognitive function models will be developed. In addition, an early life-stage zebrafish model will be developed to study neurotoxicity and behaviour development. The emphasis is on differences in exposure timing, critical windows during neuronal development and consequences on susceptibility. The underlying mechanisms of observed effects on behavior and cognitive function will also be studied. An important aspect is the development of biomarkers for (developmental) neurotoxicity in animal models using (epi-)genomics, proteomics and metabolomics.